tbuckley/cabot-search huggingface dataset:
Racial/ethnic disparities in locoregional recurrence in hormone-receptor positive node-negative breast cancer patients enrolled in the TAILORx trial.
Authors: Olga Kantor, Tari A. King, Rachel A. Freedman, Erica L. Mayer, Mariana Chavez Mac Gregor, Larissa A. Korde, Joseph A. Sparano, Elizabeth A. Mittendorf
Journal: Journal of Clinical Oncology (2022)

515 Background: Whether racial/ethnic disparities in locoregional recurrence (LRR) exist in patients (pts) with similar access to care treated on clinical trials is uncertain. We examined racial/ethnic differences in LRR in hormone-receptor positive HER2-negative (HR+HER2-) node-negative pts enrolled in the TAILORx trial. Methods: 10,273 pts age 18-75 were enrolled in TAILORx, which assigned pts with an OncotypeDx Recurrence Score (RS) &lt;11 to endocrine therapy (ET) alone, those with RS &gt;25 to chemotherapy + ET (CET), and randomized pts with RS 11-25 to ET or CET. Pts with unknown race/ethnicity (n=323) or incomplete treatment adherence information (n=1,168) were excluded from this analysis. Race/ethnicity was self-reported. LRR was defined as ipsilateral invasive in-breast, chest wall, or regional nodal recurrence without distant recurrence. Kaplan-Meier curves were used to estimate 8-year LRR. Cox proportional hazards analysis adjusted for clinical and treatment factors was used to determine factors associated with LRR. Results: 8,782 pts with T1-2N0 HR+HER2- breast cancer were included. Race/ethnicity was non-Hispanic White (NHW) in 6,932 (78.9%), non-Hispanic Black (NHB) in 629 (7.2%), Hispanic in 818 (9.3%), and Asian in 403 (4.6%). Treatment adherence was high across groups over time, with a 9.1% crossover in treatment arms. Average duration of ET was 63.8 +/- 0.3 months. Radiation therapy was planned in 96.0% of pts after breast conservation and 12.7% after mastectomy. At a median follow-up of 8 years, LRR rates were 1.9% in NHW, 4.2% in in NHB, 3.2% in Hispanic, and 3.9% in Asian pts (p&lt;0.01). LRR rates broken down by RS are shown in the Table. On adjusted analyses, NHB and Asian (vs. NHW) pts were more likely to have LRR (HR 1.94 for NHB, HR 2.04 for Asian, p&lt;0.05 for both). Additional statistically significant factors associated with LRR included age &lt;50 (HR 1.85), T2 tumors (HR 1.43), higher grade (HR 2.30 for grade 3), and high RS (HR 3.13 for RS&gt;25). Treatment receipt (chemotherapy, ET duration, and radiation) was not associated with LRR in this population. Conclusions: Racial/ethnic differences in LRR were seen in T1-2N0 HR+HER2- breast cancer pts enrolled in the TAILORx trial despite high rates of treatment adherence in this clinical trial population, with highest LRR rates in NHB and Asian pts. Further study in needed to understand racial/ethnic patterns in LRR by breast cancer subtype and if failure to rescue after LRR may contribute to differences in breast cancer mortality.[Table: see text]
Anti–PD-1 antibody (sintilimab) plus decitabine as first-line treatment for patients with higher-risk myelodysplastic syndrome (MDS): Preliminary results from a single-arm, open-label, phase II study.
Authors: Jing Wang, Siqi Li, Hao Jiang, Ying-Jun Chang, xiao-Su Zhao, jin-Song Jia, xiao-Lu Zhu, li-Zhong Gong, xiao-Hong Liu, wen-Jing Yu, xiao-Jun Huang
Journal: Journal of Clinical Oncology (2022)

7052 Background: Hypomethylating agents (HMAs) are the preferred treatment for untreated patients (pts) with higher-risk MDS, but the survival of pts after HMAs treatment is poor. It has been demonstrated that the PD-1/PD-L1 expression was upregulated by HMAs in MDS pts, providing a strong rationale for combining HMAs with PD-1 antibody for MDS treatment. Therefore, this single-arm, open-label, clinical trial was performed to evaluate safety and efficacy of Sintilimab plus decitabine for pts with higher-risk MDS (ChiCTR2100044393). Methods: Adult pts with higher-risk MDS by the IPSS-R were enrolled. Patients received decitabine 20mg/m 2 intravenously daily for 5 days and sintilimab 200mg IV starting on the first and 22nd day of a cycle every 42 days until unacceptable toxicity, relapse, or progression, for a maximum of 8 cycles. The primary endpoint was overall response rate (CR+PR+mCR). Simon’s optimal two-stage design was employed.If five or more pts in stage I (13 pts) achieved ORR, the study would enroll 34 additional pts in stage II (47 pts). Secondary endpoints included safety, and survival outcomes. The relationship between expression levels of immune-checkpoint and efficacy of the combination therapy, as well as other potential biomarkers were also explored via genomic profiling. Results: At data cut-off (January 31, 2022), 21 pts were enrolled with a median follow-up time of 5.8 months. The median age of pts was 64 years (range 30-83), and the other characteristics are summarised in Table.The ORR was 62%,with six pts reaching complete response (CR),four pts reaching marrow CR and three pts achieved marrow CR+ hematologic improvement (HI). In addition,four pts reaching HI. The most common grade 3 TEAEs( &gt; 10%) were febrile neutropenia (76.2%) and pulmonary infection (38.1%). No grade 4 TEAEs and treatment-related deaths occurred. A total of 12 pts （57.1%）experienced immune-related adverse event, including rash (28.6%), pneumonia (9.5%), hypothyroidism (9.5%), elevated serum bilirubin (4.8%) and transpeptidase (4.8%), which were all resolved by glucocorticoid. In these 21 pts, the most frequently mutated genes are ASXL1（28.6%）, RUNX1 (14.3%) and TET2(14.3%). Updated biomarker data will be presented during the ASCO meeting. Conclusions: To the best of our knowledge, this is the first study to evaluate the efficacy and safety of sintilimab plus decitabine in pts with untreated higher-risk MDS. The preliminary results demonstrate that the combination therapy is relatively safe with anti-tumor activity. Clinical trial information: ChiCTR2100044393. [Table: see text]
Tocilizumab in combination with ipilimumab and nivolumab in solid tumors.
Authors: Noha Abdel-Wahab, Emma Montazari, Christine Spillson, Salah-Eddine Bentebibel, Muhammad Awiwi, Khaled M. Elsayes, Jianjun Gao, Mehmet Altan, Michael K.K. Wong, Isabella Claudia Glitza, Rodabe Navroze Amaria, Jennifer Leigh McQuade, Sapna Pradyuman Patel, Hussein A. Tawbi, Michael A. Davies, Cassian Yee, Padmanee Sharma, James Patrick Allison, Suhendan Ekmekcioglu, Adi Diab
Journal: Journal of Clinical Oncology (2022)

TPS9600 Background: Immune checkpoint inhibitors (ICIs) are approved for multiple malignancies, however, durable remission rates with ICI monotherapy remains low. Combined treatment with anti-CTLA-4 and anti-PD1 has shown higher response rates in several cancers but is associated with up to 60% grade 3/4 immune-related adverse events (irAEs) leading to frequent treatment discontinuation. The need for corticosteroids to control irAEs may further diminish anti-tumor activity. A multi-disciplinary approach using clinical, preclinical, and translational analyses implicated the IL-6/Th17 axis in both ICI-related autoimmunity and resistance. Further, preliminary data showed that targeting interleukin 6 (IL-6) could be an effective approach to reduce irAEs while maintaining and possibly boosting the antitumor immune response. Methods: We are conducting a phase II, open-label, single center study to evaluate the use of combination treatment with tocilizumab (toci; anti-IL6), ipilimumab (ipi; anti-CTLA4) and nivolumab (nivo; anti-PD1) as a front-line therapy for patients (pts) with treatment-naïve advanced cutaneous melanoma (cohort 1), urothelial carcinoma (cohort 2), and EGFR mutant non-small cell lung cancer after tyrosine kinase inhibitors failure (cohort 3) (NCT04940299). Ten pts per disease site will be enrolled, plus an additional 25 melanoma pts in an expansion cohort. Key inclusion criteria are age ≥18 years (yrs) and histologically confirmed locally advanced or metastatic disease, with specific eligibility criteria defined for each cohort. Patients with interstitial lung diseases, autoimmune diseases, infection, or conditions requiring immunosuppressive therapies are not eligible, but stable asymptomatic brain mets are allowed. Ipi/Nivo dosing is as per approved disease indications: in cohort 1 &amp;2, ipi 3 mg/kg + nivo 1 mg/kg is administered intravenously (IV) every 3 weeks (wks) for 4 doses then nivo 480 mg/4 wks up to 2 yrs. In cohort 3, IV ipi 1 mg/kg/6 wks + nivo 3 mg/kg/2 wks is administered up to 2 yrs. In all 3 cohorts, subcutaneous (SQ) toci 162 mg/2wks is administered up to 12 wks. Imaging is every 12 wks up to 2 yrs or until dose-limiting toxicities or progression. The primary outcome is safety/tolerability of the triple therapy. The secondary outcomes are antitumor efficacy and overall survival. Additionally, tumor and blood samples are being collected for longitudinal immune analysis, including gene expression and multiplex histochemistry to identify predictive biomarkers of response, resistance, and toxicity. The trial opened in October 2021 and has enrolled 14 patients to date. Clinical trial information: NCT04940299.
A novel oral paclitaxel and HM10381 (oraxel)-treated metastatic breast cancer: A phase I study (KX-ORAX-CN-007).
Authors: Tao Qin, Xiuping Lai, Ying Wang, Jing Wang, Junyi Chen, Yiwen Zhang, Junyan Wu, Erwei Song, Herui Yao
Journal: Journal of Clinical Oncology (2022)

1104 Background: This phase I study assessed the pharmacokinetics, safety, antitumor activity of oral paclitaxel and HM10381 (Oraxel) in patients with metastatic breast cancer. Methods: Oraxol (oral paclitaxel 205 mg/m 2 plus HM30181A 15 mg) daily for 3 consecutive days weekly for up to 16 weeks was administered to patients. The primary objective endpoint was pharmacokinetic analysis. The secondary endpoint were objective response rate (ORR) and safety. For pharmacokinetic analysis, timed blood samples were collected. Results: Twenty-four female patients were enrolled from Apr 2019 to Aug 2019. The median age was 53 years (range: 35 to 70 years). The mean lines and median line of treatment were 2.5 and 2, respectively. Previous breast cancer treatments included chemotherapy in 23 (96%) patients, hormonal therapy in 20 (83%) patients. Prior taxanes therapy was reported in 20 (83%) patients. There were 15 patients in efficacy dataset. The best ORR (Investigator) was PR in 40%, SD in 53%, and PD in 7%. The best overall response rate (ICRRC) was PR in 36%, SD in 57%, and PD in 7% of patients. There were no hypersensitivity-type reactions. Adverse events of interest neutropenia, neurotoxicity, and diarrhea were reported as 20 (83%)，7 (29%) and 11 (46%), retrospectively. A total of 15 (63%) patients experienced Grade ≥3 TEAEs, including neutrophil count decreased in 11 (46%) patients, WBC count decreased in 8 (33%) patients. Treatment related SAE was reported in 1 (4.17%) patient experienced febrile neutropenia, pneumonia, and septic shock. The PK data indicated that the efficacy response is not associated with oral paclitaxel exposure parameters AUC or Cmax. Conclusions: The study showed that Oraxol as novel oral chemotherapy agent shows promising antitumor activity in patients with metastatic breast cancer, manageable toxicity, and no hypersensitivity-type reactions. Clinical trial information: NCT04993040.
Incidence of chronic graft versus host disease using post-transplant cyclophosphamide in HLA-matched versus haploidentical donors.
Authors: Mary Moses Hitt, Wondwosen Yimer, Carter Payne Milner, Vincent E. Herrin, Stephanie Elkins, Carolyn L. Bigelow, Talal Hilal
Journal: Journal of Clinical Oncology (2022)

e19044 Background: Allogeneic hematopoietic cell transplant (allo-HCT) is the only potential cure for many hematologic cancers. Graft-versus-host disease (GVHD) is a significant cause of mortality after allo-HCT. Post-transplant cyclophosphamide (PTCy) in haploidentical HCT (haplo-HCT) has yielded survival outcomes similar to those seen in HLA-matched allo-HCT. Single center studies have demonstrated lower rates of chronic GVHD with the use of PTCy in HLA-matched allo-HCT. In this single center study, we analyzed the outcomes of HLA-matched and haplo-HCT in patients (pts) who received PTCy for GVHD ppx. Methods: Pts who received allo-HCT from matched related (MRD), matched unrelated (MUD), and haploidentical donors (Haplo) from Jan 2016 to July 2021 were identified. Pts who did not receive PTCy were excluded. Pts were divided into two groups – MRD/MUD and Haplo. Primary endpoint was cumulative incidence of chronic GVHD. Secondary endpoints were cumulative incidence of relapse, non-relapse mortality (NRM), and overall survival (OS) at 2-years. Comparisons were made based on log-rank test and a model for subhazard function of a failure event of primary interest with p &lt; 0.05 used as cut-off point for statistical significance. Results: 62 pts (45 MRD/MUD,17 Haplo) were included. Baseline characteristics were similar. Median follow-up was 342 days post-transplant. Most had a diagnosis of AML (50%), high/very high DRI (48%), and received RIC (55%). Cumulative incidence of chronic GVHD was 11% overall (95% CI 5.8-21.3%); 6% for MRD/MUD and 27% for Haplo (p = 0.045). Cumulative incidence of relapse was 28% overall (95% CI 18-42%); 34% for MRD/MUD and 13% for Haplo (p = 0.09). Two-year OS was 55% overall (95% CI 39.1- 68.7%); 53% for MRD/MUD and 61% for Haplo (p = 0.043). There was no significant difference in incidence of grade 2-4 acute GVHD or NRM between groups. Conclusions: PTCy resulted in a significantly lower incidence of chronic GVHD in MRD/MUD group compared to Haplo group. Although cumulative incidence of relapse was not statistically different between groups, OS was worse in the MRD/MUD allo-HCT group after PTCy and most deaths were due to relapse.[Table: see text]
Pembrolizumab + chemotherapy in patients with persistent, recurrent, or metastatic cervical cancer: Subgroup analysis of KEYNOTE-826.
Authors: Krishnansu Sujata Tewari, Nicoletta Colombo, Bradley J. Monk, Coraline Dubot, M. Valeria Cáceres, Kosei Hasegawa, Ronnie Shapira-Frommer, Pamela Salman, Eduardo Yañez, Mahmut Gumus, Mivael Olivera Hurtado de Mendoza, Vanessa Samouëlian, Vincent Castonguay, Alexander Arkhipov, Cumhur Tekin, Kan Li, Sarper Toker, Stephen Michael Keefe, Domenica Lorusso
Journal: Journal of Clinical Oncology (2022)

5506 Background: In KEYNOTE-826 (NCT03635567),pembrolizumab (pembro) + chemotherapy (chemo) ± bevacizumab (bev) provided statistically significant, clinically meaningful PFS and OS improvements in patients with persistent, recurrent, or metastatic cervical cancer. In the present analysis of KEYNOTE-826, we assessed outcomes in several key patient subgroups. Methods: Eligible adult patients had persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix not previously treated with chemo and not amenable to curative treatment; measurable disease per RECIST v1.1; ECOG PS 0–1; and a tumor sample to determine PD-L1 status. Patients were randomized 1:1 to pembro 200 mg Q3W or placebo (pbo) for up to 35 cycles + chemo (paclitaxel 175 mg/m 2 + cisplatin 50 mg/m 2 or carboplatin AUC 5) ± bev 15 mg/kg. Dual primary endpoints are PFS by investigator assessment per RECIST v1.1 and OS in patients with PD-L1 CPS ≥1, all comers, and CPS ≥10. Treatment effects on PFS and OS were examined in patient subgroups defined by bev use (yes or no), histology (squamous or non-squamous [including adenocarcinoma and adenosquamous]), platinum use (carboplatin or cisplatin), and prior chemoradiation therapy (CRT). Hazard ratios (HR) and 95% CIs were based on a stratified Cox regression model. Results: 617 patients were randomized (pembro + chemo ± bev, n=308; pbo + chemo ± bev, n=309). At the May 3, 2021 data cutoff, median follow-up was 22 months. Pembro + chemo prolonged PFS and OS vs pbo + chemo in all subgroups evaluated in the all-comer population (Table). Similar benefits of pembro + chemo on PFS and OS were also seen in the protocol-specified CPS ≥1 and CPS ≥10 populations. Conclusions: Pembro + chemo ± bev prolonged PFS and OS vs pbo + chemo ± bev among the subgroups defined by bev use, histology, platinum use, and prior CRT and provided clinically meaningful benefits similar to the broader population of patients with persistent, recurrent, or metastatic cervical cancer. Clinical trial information: NCT03635567. [Table: see text]
Molecular classification for predicting the efficacy of neoadjuvant tislelizumab combining nab-paclitaxel in Chinese bladder cancer.
Authors: Hailong Hu, Yuanjie Niu, HaiTao Wang, Huanhuan Liu, Chong Shen, La Da, Gangjian Zhao, Lili Wang, Zhouliang Wu, Shanbo Cao, Feng Lou, Huina Wang
Journal: Journal of Clinical Oncology (2022)

e14563 Background: Bladder cancer is a molecularly diverse disease with heterogeneous clinical outcomes. Transcriptome-based molecular subtypes of muscle invasive bladder cancer (MIBC) and non-muscle invasive bladder cancer (NMIBC) have been shown to be both prognostic and predictive. However, its predictive role in Chinese bladder cancer remains unclear. The aim of this study was to identify the predictive role of molecular subtypes in China bladder cancer with neoadjuvant therapy. Methods: The study was conducted from May 2020 to August 2021. Patients who were age 18 years or older, were diagnosed with NMIBC or MIBC, and neoadjuvant tislelizumab combining nab-paclitaxel followed by surgery were included. Multigenomic sequencing was performed. Molecular subtypes were identified by published consensus. Results: We prospectively recruited 30 patients for neoadjuvant tislelizumab combining nab-paclitaxel, including 14 patients with NMIBC and 16 patients with MIBC. For bladder cancer, 73.3% (22/33) patients responded to neoadjuvant tislelizumab combining nab-paclitaxel. In NMIBC groups, 64.3% (9/14) patients were pCR. The objective remission rate ( ORR) was 71.4%. 4 molecular classes were identified in Chinese NMIBC, including class 1 (7.1%), class 2a (35.7%), class 2b (50%), class 3 (7.1%). Interesting, ORR was significantly higher for patients with class 2b (5/7, 71.4%) as compared to class 2a (3/5,60%) before neoadjuvant. Molecular classes changed in 35.7% (5/14) of patients before and after neoadjuvant. After neoadjuvant, 80% of class 2b patients responded to neoadjuvant, and all class 2a patients did not respond to neoadjuvant. In MIBC groups, a pPR was achieved by 37.5% patients (6/16). The ORR was 75%. We found 4 molecular classes in Chinese MIBC: basal/squamous (43.8%), luminal unstable (25%), luminal papillary (25%), and stroma-rich (6.2%). Patients with basal/squamous (85.7%) and luminal unstable (75%) had significantly higher ORR than luminal papillary (50%) before neoadjuvant. Molecular classes changed in 44.4% (4/9) of patients before and after neoadjuvant. After neoadjuvant, all patients with stroma-rich responded to neoadjuvant. Conclusions: Molecular classification could predict the efficacy of neoadjuvant tislelizumab combining nab-paclitaxel in Chinese bladder cancer, which may be preferable when studying biomarkers of bladder cancer in the future.
Efficacy of nivolumab and temozolomide in advanced neuroendocrine neoplasms (NENs) in a phase 2 clinical trial.
Authors: Dwight Hall Owen, Brooke Benner, Lai Wei, Vineeth Sukrithan, Ashima Goyal, Ye Zhou, Sheryl-Ann Suffren, Carly Pilcher, Gwen Christenson, Nancy Curtis, Himanshu Savardekar, Ruthann Norman, Sarah Ferguson, Barbara Kleiber, Robert Wesolowski, William Edgar Carson, Gregory Alan Otterson, Claire F. Verschraegen, Manisha H. Shah, Bhavana Konda
Journal: Journal of Clinical Oncology (2022)

4121 Background: Treatment options are limited in patients with metastatic NEN. Temozolomide (TEM) alone and in combination with capecitabine is active in NEN and has been shown to have immunomodulatory impact. Here we present the final results for the NEN cohort of a phase 2 trial of combination nivolumab and TEM in patients with advanced NEN along with observed peripheral immune changes. Methods: NCT03728361 is a non-randomized, two-cohort, open-label phase 2 trial of nivolumab and TEM in patients with metastatic NEN and small cell lung cancer. The NEN cohort enrolled patients with tumors of any WHO grade, location, and line of therapy; all patients had evidence of progression prior to study. Prior immunotherapy was not allowed. Treatment consisted of nivolumab 480 mg IV on day 1 and TEM 150 mg/m2 on days 1-5 of a 28-day cycle. The primary objective was efficacy measured as response rate (RR) by RECIST v1.1. Secondary objectives were progression free survival (PFS) and overall survival (OS), by the method of Kaplan–Meier. The translational objective was to analyze peripheral blood mononuclear cells (PBMCs) collected at screening (baseline) and on cycle 1, day 15 (C1D15) via mass cytometry. Results: The RR was 36% (n=10/28, 95% CI: 18.6%-55.9%), including 10 patients (36%) with PR, 16 (57%) with SD, and 2 (7%) with PD (Table). The disease control rate was 93%. Responses occurred across all WHO grades; 44% of patients with tumors with Ki-67 &gt;20% had PR. There was a significant difference in ORR by primary tumor location (bronchial vs pancreas vs other, p=0.004). There was no significant difference in response by Ki-67% (p=0.872), or in patients treated as first line (31%) or beyond (40%, p=0.706). The median PFS was 8.9 months (95% CI: 3.9 – 11.1 months), and median OS was not reached (95% CI: 20.7 – NR months). Two immune related SAE’s occurred: myocarditis and diarrhea in one patient each; gr4 toxicities included neutropenia (10%) and thrombocytopenia (7%). Profiling of PBMCs revealed no correlation of baseline MDSC levels with clinical benefit, however significant changes within the T cell landscape, including a decrease in CD4+ T cells (59.6% ±13.08 vs. 56.5% ±13.01, p=0.001) and increase in CD8+ T cells (27.9% ±13.36 vs. 31.7% ±14.57, p=0.03) were observed. Conclusions: Combination nivolumab and TEM demonstrated promising efficacy in patients with NENs; median OS has not been reached. Clinical trial information: NCT03728361. [Table: see text]